Method for the continuous production and coating of self-adhesive compounds on the basis of sbc that includes at least one pharmaceutically active substance

ABSTRACT

A process for the solvent-free and mastication-free production of a self-adhesive composition which is based on SBC and comprises a pharmaceutically active substance, in a continuously operating apparatus which comprises a feeding section and a compounding section. The SBC is added to the feeding section and the pharmaceutically active substance is added to the feed section and/or the compounding section, and the composition is homogenized in the compounding section.

The present invention relates to a method for the continuous productionand coating of self-adhesive compositions based on SBC with at least onepharmaceutically active substance.

Fundamental to the profile of performance requirements of pressuresensitive adhesive systems and the pressure sensitive adhesive articlesproduced with them (such as patches, for example) are the two physicalphenomena of adhesion and cohesion of the pressure sensitive adhesivelayers. Adhesion is dealt with in the technical jargon using the termsinstant bond strength (tack) and bond strength (peel strength) anddescribes by definition the terms “self-adhesive”, “pressure sensitiveadhesive” and/or “pressure sensitive adhesive tapes”, i.e., permanentadhesive bonding under “gentle applied pressure”.

Especially in the case of pressure sensitive adhesives based on rubber,this property is obtained by mixing in tackifying resins (tackifiers)and plasticizers having relatively low molecular weights.

The second defining property of the pressure sensitive adhesives istheir simple residue-free redetachability after use. This property isdetermined essentially by the high molecular mass rubber fractions asthe elastomer component, which give the system, in the form of cohesion(internal strength), the required strength under shear stress, which isof particular significance for the use of the products under mechanicalload.

The performance of the pressure sensitive adhesive is, therefore,critically determined by the balanced proportion of adhesion propertiesand cohesion properties and by compatibility, homogeneity, and stabilityof the blend of components with extremely high and relatively lowaverage molecular weights, something which is relatively easy to achievewhen the composition is produced in industry-standard mixers andkneading machines using solvents.

The advantage of foregoing the use of solvents lies essentially in thesimplification of the coating method. The avoidance of flammablesolvents does away with the need for the drier units, with their highenergy consumption for the evaporation and recovery of the solvents, andwith the need to use explosion-protected units. Hot-melt coating unitsare compact and permit much higher coating speeds. The technology is anenvironment-friendly one in which there are no solvent emissions.Furthermore, no unwanted solvent residues remain in the self-adhesivecomposition. This is the reason for the reduction in the allergenicpotential of the product.

For solvent-free compounding, the prior art makes use predominantly ofblock copolymers having polystyrene block fractions, or natural and/orsynthetic rubbers.

Owing to the high molecular mass fractions of the rubber (withM_(W)≧3*10⁵ g/mol), solvent-free natural rubber self-adhesivecompositions cannot be processed by the hot-melt pressure sensitiveadhesive technology, or else the rubbers used must be reduced in theirmolecular weight (broken down) severely before processing.

The deliberate industrial process of rubber breakdown under the combinedaction of shear stress, temperature, and atmospheric oxygen is referredto in the technical literature as mastication and is generally carriedout in the presence of chemical auxiliaries, which are known from thetechnical literature as masticating agents or peptizers, or, morerarely, as “chemical plasticizing agents”.

In rubber technology, the mastication step is necessary in order to makeit easier to integrate the additives.

Mastication is a term used in rubber technology for the breaking down oflong-chain rubber molecules in order to increase the plasticity and/orreduce the (Mooney) viscosity of rubbers. Mastication is carried out bytreating, in particular, natural rubber in kneading apparatus or betweenrolls at very low temperatures in the presence of mastication aids(masticating auxiliaries). The high mechanical forces which act lead toa “tearing apart” of the rubber molecules, with the formation ofmacroradicals, whose recombination is prevented by reaction withatmospheric oxygen. Mastication aids such as aromatic or heterocyclicmercaptans and their zinc salts or disulfides accelerate the masticationprocess by promoting the formation of primary radicals. Activators suchas metal (iron, copper, cobalt) salts of tetraazaporphyrins orphthalocyanines enable the mastication temperature to be lowered. Forthe mastication of natural rubber, mastication aids are used in amountsof from about 0.1 to 0.5% by weight in the form of masterbatches, whichfacilitate a uniform distribution of this small amount of chemicalswithin the rubber composition.

Mastication must be clearly distinguished from the breakdown known asdegradation which results in all of the standard solvent-free polymertechnologies, such as compounding, conveying, and coating in the melt.

Degradation is a collective term for various processes which change theappearance and properties of plastics. Degradation may be caused, forexample, by chemical, thermal, oxidative, mechanical or biologicalinfluences or else by the effect of rays (such as (UV) light). Examplesof consequences are oxidation, chain cleavages, depolymerization,crosslinking, and/or elimination of side groups of the polymers. Thestability of polymers with respect to degradation may be increased byusing additives, for example, by adding stabilizers such as antioxidantsor light stabilizers.

A variety of routes to the solvent-free production and processing ofrubber pressure sensitive adhesives have been described.

The patent CA 698 518 describes a process for producing a composition byadding high proportions of plasticizer and/or by simultaneously strongmastication of the rubber. Although this method may be used to obtainpressure sensitive adhesives having an extremely high tack, auser-compatible shear strength can be achieved only to a limited extent,even with a relatively high level of subsequent crosslinking, owing tothe relatively high plasticizer content or else to the severe breakdownin molecular structure of the elastomer to a molecular weight average ofM_(W)≦1 million.

The use of polymer blends, where, besides nonthermoplastic naturalrubber, use is also made of block copolymers, in a ratio ofapproximately 1:1, is essentially an unsatisfactory compromise solution,since it results neither in high shear strengths when the self-adhesivetapes are used at relatively high temperatures nor in significantimprovements relative to the properties described in the patent.

The use of exclusively non-thermoplastic rubbers as the elastomercomponent in the formulation of pressure sensitive adhesives with theexisting cost advantage possessed by, for example, natural rubbers overthe standard commercial block copolymers, and the outstandingproperties, especially the shear strength of natural rubber and ofcorresponding synthetic rubbers, is also set out at length in thepatents WO 94 11 175 A1, WO 95 25 774 A1, and WO 97 07 963 A1 and,correspondingly, U.S. Pat. Nos. 5,539,033 A and 5,550,175 A.

In these cases, the additives customary in pressure sensitive adhesivetechnology, such as tackifier resins, plasticizers, and fillers, aredescribed.

The production method disclosed in each case is based on a twin screwextruder which permits compounding to a homogeneous pressure sensitiveadhesive blend with the chosen process regime, involving mastication ofthe rubber and subsequent gradual addition of the individual additiveswith an appropriate temperature regime.

The mastication step of the rubber, which precedes the actual productionprocess, is described at length. It is necessary and characteristic ofthe process chosen, since with the technology chosen therein it isindispensable to the subsequent integration of the other components andto the extrudability of the blended composition. Also described is thefeeding in of atmospheric oxygen, as recommended by R. Brzoskowski, J.L. and B. Kalvani in Kunststoffe 80 (8), (1990), p. 922 ff., in order toaccelerate mastication of the rubber.

This procedure makes it absolutely necessary to practice the subsequentstep of curing by electron beam crosslinking (EBC) and to use reactivesubstances as EBC promoters in order to achieve an effectivecrosslinking yield.

Both method steps are described in the abovementioned documents, but theEBC promoters chosen also tend toward unwanted chemical crosslinkingreactions at elevated temperatures. This limits the use of certaintackifying resins and the use of the self-adhesive compositionsproduced, in particular for pharmaceutical applications.

It is an object of the present invention to provide a method with whichself-adhesive compositions based on SBC and comprising at least oneactive pharmaceutical substance can be produced continuously withoutsolvent and, if desired, can be coated in-line without the need forproperty-impairing mastication of the SBC.

This object is achieved by a method as set out in claim 1. Claim 2describes a variant of the method of the invention. The dependent claimsrelate to advantageous developments of the methods.

The invention accordingly provides a method for the continuoussolvent-free and mastication-free production of self-adhesivecompositions based on SBC with at least one pharmaceutically activesubstance in a continuously operating apparatus having a filling sectionand a compounding section, comprising the following steps:

-   a) feeding an initial batch comprising SBC, optionally a release    auxiliary and at least one active pharmaceutical substance into the    filling section of the apparatus; if desired, feeding low molecular    weight SBC, fillers, plasticizers, tackifiers, resins and/or    additives,-   b) transferring the feed components of the self-adhesive composition    from the filling section to the compounding section,-   c) if desired, adding the components of the self-adhesive    composition that have not been introduced in the filling section,    such as low molecular mass SBC, fillers, plasticizers, tackifiers,    resins and/or additives, to the compounding section,-   d) if desired, adding further active pharmaceutical substances to    the compounding section of the apparatus,-   e) preparing a homogeneous self-adhesive composition in the    compounding section, and-   f) discharging the self-adhesive composition.

The invention additionally embraces a method for the continuoussolvent-free and mastication-free production of self-adhesivecompositions based on SBC with at least one pharmaceutically activesubstance in a continuously operating apparatus having a filling sectionand a compounding section, comprising the following steps:

-   a) feeding SBC, optionally with a release auxiliary into the filling    section of the apparatus; if desired, feeding low molecular weight    SBC, fillers, plasticizers, tackifiers, resins and/or additives,-   b) transferring the feed components of the self-adhesive composition    from the filling section to the compounding section,-   c) adding at least one active pharmaceutical substance to the    compounding section and, if desired, adding the components of the    self-adhesive composition that have not been introduced in the    filling section, such as low molecular mass SBC, fillers,    plasticizers, tackifiers, resins and/or additives, to the    compounding section,-   d) preparing a homogeneous self-adhesive composition in the    compounding section, and-   e) discharging the self-adhesive composition.

The addition of at least one active pharmaceutical substance to thecompounding section, and the possibly necessary addition to thecompounding section of components of the self-adhesive composition whichhave not been introduced in the filling section, such as low molecularweight SBC, fillers, plasticizers, tackifiers, resins and/or additives,may take place over the entire length of the compounding section. Inparticular, a plurality of metering points are possible, so that eachindividual component may be metered in specifically via a separate feeddepending on the requirements of the operating regime.

It has been found particularly advantageous to use a twin screw extruderhaving at least one metering port, preferably between two and seven, andat least one devolatilization port, as the continuously operatingapparatus. This twin screw extruder allows short mixing times and thusvery gentle processing of the composition, particularly ofheat-sensitive components used.

The temperature in the apparatus should be maintained at 85-120° C.,preferably 85 to 110° C., with particular preference 85 to 100° C., inorder to rule out thermal damage to, in particular, the active substanceor substances.

In one advantageous embodiment of the method, a melt pump or an extruderfor conveying the self-adhesive compositions is arranged between theapparatus and the coating device.

In the second method step, which takes place advantageously inintegration with the compounding step in the twin screw extruder, theself-adhesive composition prepared in accordance with the invention iscoated in a solvent-free manner onto a backing in web form, onto arelease film or onto a release paper, using an applicator unit. Coatingmay take place over the full area or else partially.

In order to obtain a defined, air-bubble-free application of compositionto the web-form material, it is advantageous for the self-adhesivecomposition to be subjected to devolatilization before entering thecoating unit, something which is particularly important when inert gasesare used during the compounding operation in the twin screw extruder.

In accordance with the process of the present invention,devolatilization may take place under the influence of subatmosphericpressure or to the atmosphere preferably in screw machines.

Various methods are suitable for coating onto web-form materials.Solvent-free self-adhesive compositions may be coated by means of anextrusion die downstream of the twin screw extruder. For the pressurebuildup for die coating, single screw extruders and/or melt pumps areparticularly preferred, so that the web-form backing materials may becoated with composition application rates with a very low breadth offluctuation.

A further possibility for coating web-form backing materials with theactive substance self-adhesive composition prepared in accordance withprocesses of the invention is the use of roll coating applicator unitsor multiroll coating calenders, consisting preferably of at least twocoating rolls, the self-adhesive composition being formed to the desiredthickness as it passes through one or more roll nips prior to transferto the web-form material. This coating method is particularly preferredwhen coating with extrusion dies alone no longer provides the requiredaccuracy in the amount of composition applied.

Depending on the nature of the web-form backing material to be coated,coating may take place by a co-rotational or counter-rotational method.

Coating is possible on roll coating applicator units or multirollcoating calenders at temperatures below 120° C., so that it is alsopossible to coat self-adhesive compositions which comprise thermallysensitive active substances. For the purpose of increased gas bubblefreedom of the coated adhesive composition, it is possible to install avacuum devolatilizer, for example, a vacuum chamber, a devolatilizingextruder, air knives or the like, between twin screw extruder andapplicator unit.

In accordance with the method of the present invention, there is noproperty-impairing mastication of the SBC, since the melting of thephysically crosslinked styrene domains takes place shortly after the SBCis introduced.

The twin screw extruder should have one or, preferably, a plurality ofseparate temperature control or cooling circuits in order to permit atemperature regime which allows the use of thermally sensitive activepharmaceutical substances. In cases where this is unnecessary, thetemperature control circuits may also be combined with one another inorder to keep the number of temperature control devices as low aspossible.

The method of the invention permits the preparation of self-adhesivecompositions with active pharmaceutical substances and, especially inconjunction with a downstream coating unit, the production ofself-adhesive articles which in turn are used to produce patches orbandages, while achieving particular cost advantages.

The method consists essentially of the steps set out already, whichoptionally may be conducted under an inert gas atmosphere in order toprevent oxidative polymer degradation.

In the compounding step, an adhesive composition comprising styreneblock copolymers, one or more active pharmaceutical substances, and therequired adjuvants such as low molecular mass SBC, fillers,plasticizers, tackifiers, resins and/or additives, is produced withoutsolvent preferably in a twin screw extruder. The active pharmaceuticalsubstances here may be added directly at the beginning of the method,but may also—depending on the sensitivity of the active substance—beintroduced into the twin screw extruder only at a later point in time.The addition may be made in neat or dissolved form.

In accordance with the invention, the hot-melt self-adhesive compositionin which at least one active pharmaceutical substance is incorporated,is based on

-   -   phase-separating styrene block copolymers,    -   tackifying resins,    -   tackifiers,    -   plasticizers,    -   fillers and/or additives.

Suitable styrene block copolymers include preferably A-B and/or A-B-Ablock copolymers or mixtures thereof. The hard, domain-forming phase Aconsists primarily of polystyrene or derivatives thereof. The soft phaseis formed primarily from polyisoprene and polybutadiene or mixturesthereof. The phase-separating structure of the styrene block copolymershelps the polymers have a thermoplastic behavior which differs from thatof polymers containing randomly distributed monomers and ensuresmastication-free processing. Owing to the incompatibility of the Ablocks and B blocks, the block copolymers possess two glass transitiontemperatures T_(g): as a result of the B blocks, a low T_(g,) below roomtemperature, and, as a result of the styrene blocks, a high T_(g,) aboveroom temperature. In the temperature range between the two glasstransition temperatures the block copolymers exhibit on the one handelastic behavior as a result of the B blocks, but on the other hand therubber remains cohesive as a result of the hard styrene domains, whichcome about as a result of secondary valence forces of the styreneblocks.

The fraction of the styrene block copolymers is between 5 and 90% byweight, preferably between 10 and 85% by weight.

Suitable fillers are free-flowing bulk materials and also mixturesthereof, such as cellulose, silica, alginates and pectins, which are notsoluble in the adhesive matrix.

The filler fraction is in particular between 0% by weight and 60% byweight, preferably between 0% by weight and 40% by weight, withparticular preference between 0% by weight and 30% by weight.

Tackifying resins which can be used are, without exception, alltackifier resins known to date and described in the literature.Representatives that may be mentioned include the rosins, theirdisproportionated, hydrogenated, polymerized and esterified derivativesand salts, the aliphatic and aromatic hydrocarbon resins, terpene resinsand terpene-phenolic resins. Any desired combinations of these and otherresins can be used in order to adjust the properties of the resultantadhesive composition in accordance with what is desired. Reference maybe made expressly to the depiction of the state of knowledge in“Handbook of Pressure Sensitive Adhesive Technology” by Donatas Satas(van Nostrand, 1989).

The resin fraction is in particular between 0% by weight and 80% byweight, preferably between 0% by weight and 60% by weight, withparticular preference between 10% by weight and 50% by weight.

Hydrocarbon resin is a collective term for thermoplastic polymers whichare colorless to intense brown in color and have a molar mass ofgenerally <2 000.

They may be divided into three main groups according to theirprovenance: petroleum resins, coal tar resins, and terpene resins. Themost important coal tar resins are the coumarone-indene resins. Thehydrocarbon resins are obtained by polymerizing the unsaturatedcompounds that can be isolated from the raw materials.

Included among the hydrocarbon resins are also polymers obtainable bypolymerizing monomers such as styrene and/or by means ofpolycondensation (certain formaldehyde resins), with a correspondinglylow molar mass. Hydrocarbon resins are products with a softening rangethat varies within wide limits from <0° C. (hydrocarbon resins liquid at20° C.) to >200° C. and with a density of from about 0.9 to 1.2 g/cm³.

They are soluble in organic solvents such as ethers, esters, ketones,and chlorinated hydrocarbons, and insoluble in alcohols and water.

By rosin is meant a natural resin which is recovered from the cruderesin from conifers. Three types of rosin are differentiated: balsamresin, as a distillation residue of turpentine oil; root resin, as theextract from conifer rootstocks; and tall resin, the distillationresidue of tall oil. The most significant in terms of quantity is balsamresin.

Rosin is a brittle, transparent product with a color ranging from red tobrown. It is insoluble in water but soluble in many organic solventssuch as (chlorinated) aliphatic and aromatic hydrocarbons, esters,ethers, and ketones, and also in plant oils and mineral oils. Thesoftening point of rosin is situated in the range from approximately 70to 80° C.

Rosin is a mixture of about 90% resin acids and 10% neutral substances(fatty acid esters, terpene alcohols, and hydrocarbons). The principalrosin acids are unsaturated carboxylic acids of empirical formulaC₂₀H₃₀O₂, abietic acid, neoabietic acid, levopimaric acid, pimaric acid,isopimaric acid, and palustric acid, as well as hydrogenated anddehydrogenated abietic acid.

The proportions of these acids vary depending on the provenance of therosin.

Suitable tackifiers are all known tackifying polymers, from the group,for example, of the polyisoprenes and polybutadienes. The tackifierfraction is in particular between 0% by weight and 50% by weight,preferably between 0% by weight and 40% by weight, with particularpreference between 0% by weight and 30% by weight.

Plasticizers which can be used are all known plasticizing substances andalso pharmaceutical auxiliaries. They include, inter alia, theparaffinic and naphthenic oils, (functionalized) oligomers such asoligobutadienes and oligoisoprenes, liquid nitrile rubbers, liquidterpene resins, vegetable and animal oils and fats, fatty acid esters,phthalates, alcohols, and functionalized acrylates.

The plasticizer fraction is in particular between 0% by weight and 60%by weight, preferably between 2% by weight and 40% by weight.

Additives used can include aging inhibitors or stabilizers. Thereinclude, for example, sterically hindered phenols, hydrolysis-stablephosphites and organosulfur compounds. The additive fraction is between0% and 5% by weight, preferably between 0% and 3% by weight.

Active pharmaceutical substances are substances which in human or animalorganisms are used to prevent, heal, alleviate or detect diseases. Theactive pharmaceutical substances used may include those having bothsystemic and local activity.

Typical active substances used in accordance with the invention are thefollowing: aceclidine, amphetaminil, amphetamine, amyl nitrite,apophedrine, atebrine, alprostadil, azulene, arecoline, anethole,amylene hydrate, acetylcholine, acridine, adenosine-triphosphoric acid,malic acid, alimemazine, allithiamine, aminoethanol, apyzine, apiole,azatadine, alprenolol, ethinazone, bisabolol, bisnorephedrine,butacetoluide, benactyzine, camphor, colecalciferol, chloral hydrate,clemastine, chlorobutanol, capsaicin, cyclopentamine, clobutinol,chamazulene, dimethocaine, codeine, chlorpromazine, quinine,chlorothymol, cyclophosphamide, cinchocaine, chlorambucil,chlorphenesin, dexchlorpheniramine, dinoprostone, dixyrazine, ephedrine,ethosuximide, enallylpropymal, emylcamate, erythrol tetranitrate,emetine, eucalyptol, etofenamate, ethylmorphine, fentanyl, fluanisone,guaiazulene, hyoscyamine, histamine, fencarbamide, hydroxycaine,hexylresorcinol, isoaminile citrate, isosorbide dinitrate, ibuprofen,iodine, iodoform, isoaminile, lidocaine, lopirine, levamisole,methadone, methyprylon, methylphenidate, mephenesin, methylephedrine,meclastine, methopromazine, mesuximide, menthol, methylpentynol,metixene, mesoprostol, nikethamide, norpseudoephedrine, nonylicvanillylamide, oxytetracaine, oxyprenolol, oxyphenbutazone,oxyquinoline, pinene, prolintane, procyclidine, piperazine, pivazide,phensuximide, procaine, phenindamine, promethazine, pentetrazole,profenamine, perazine, phenol, pethidine, pilocarpine, prenylamine,phenoxybenzamine, resochine, scopolamine, salicylic acid, sparteine,timolol, trifluperazine, tetracaine, trimipramine, tranylcypromine,trimethadione, tybamate, thymol, thioridazine, valproic acid andverapamil, and also other active substances familiar to the skilledworker that can be absorbed through the skin, including the mucousmembranes. This list is of course not exhaustive.

Particularly important active substances will now be listed andclassified in more detail—here again without claiming completenesswithin the context of the present invention: Indication: Activesubstance Antimycotics Naftifine((E)-N-Cinnamyl-N-methyl-1-naphthalenemethanamine)

Amorolfine ((±)-cis-2,6-Dimethyl-4-[2-methyl-3-(4-tert-pentylphenyl)propyl]morpholine)

Tolnaftate (O-(2-Naphthyl)-N-methyl-N-m-tolyl-thiocarbamate)

Clotrimazole (1-[(2-Chlorophenyl)diphenylmethyl]-1H-imidazole)

Antiseptics Triclosan Ethacridine Chlorhexidine Hexetidine DodicinIodine Non-steroidal Methyl salicylate anti- Etofenamate inflammatoryIndomethacin drugs ([1-(4-Chlorobenzoyl)-5-methoxy-2-methyl-1H-indol-3-yl]acetic acid

Antipruritics Crotamiton Local Benzocaine anesthetics AntipsoriaticsKeratolytics Urea

Further active substances which promote wound healing, such as silversulfadiazene, can likewise be employed.

With particular advantage and in the context of the invention it is alsopossible to mention hyperemic active substances such as natural activesubstances from cayenne pepper or synthetic active substances such asnonivamide, nicotinic acid derivatives, preferably benzyl nicotinate orpropyl nicotinate, and antiinflammatories and/or analgesics.

By way of example mention may be made of capsaicin

[-Methyl-trans-6-nonenoic acid (4-hydroxy-3methoxybenzlamide)]

Nonivamide

Nicotinic acid benzyl ester

Among the active substances, the disinfectants and antiseptics should beemphasized as being particularly important, and so their use is to beemphasized again.

Substances designated disinfectants are those suitable for disinfection,i.e., for controlling pathogenic microorganisms (for example, bacteria,viruses, spores, microfungi and molds), in particular generally by useon the surface of skin, clothing, equipment, rooms, but also drinkingwater, foodstuffs, seed (dressing) and as soil disinfectants.

Disinfectants particularly for local use, for disinfecting wounds forexample, are also referred to as antiseptics.

As an antiseptic use may be made in particular of the lactic acidderivatives, such as esters and also oligolactic and polylactic acid.

Known lactic esters include the esters, frequently named as lactates ofthe respective alcohol component, of the general formula

the majority of which are products which have low melting points or areliquid at 20° C. and which, with the exception of the lower alkylesters, are sparingly soluble in water but readily soluble in alcoholand ether.

The following lactic esters are differentiated:

-   (a) lactic acid methyl ester (methyl lactate), C₄H₈O₃, M_(r) 104.10,    boiling point 145° C.-   (b) lactic acid ethyl ester (ethyl lactate), C₅H₁₀O₃, M_(r)    118.13, D. 1.03, boiling point 154° C.-   (c) lactic acid isopropyl ester (isopropyl lactate), C₆H₁₂O₃, M_(r)    132.15, D. 0.9980, boiling point 167° C.-   (d) lactic acid butyl ester (butyl lactate), C₇H₁₄O₃, M_(r)    146.18, D. 0.9803, boiling point 187° C.

Polylactic acid (polylactide) is a polyester based on lactic acid, fromwhose lactide it can be prepared by means of ring-openingpolymerization.

The active substance fraction in the self-adhesive composition ispreferably between 0.001% by weight and 0.7% by weight, more preferablybetween 0.01% by weight and 0.67% by weight, with particular preferencebetween 0.03% by weight and 0.63% by weight.

Depending on the intended use, suitable web-form backing materials forthe self-adhesive compositions processed and produced in accordance withthe invention are all known backings, with or without appropriatechemical or physical surface pretreatment of the coating side, and alsoanti-adhesive physical treatment or coating of the reverse side. Mentionmay be made, for example, of creped and noncreped papers, polyethylene,polypropylene and mono- or biaxially oriented polypropylene films,polyester, PVC and other films, foam materials in web form, made frompolyethylene and polyurethane, for example.

Another suitable example is a metallocene polyethylene nonwoven.

The metallocene polyethylene nonwoven preferably has the followingproperties:

-   -   a basis weight of from 40 to 200 g/m², in particular from 60 to        120 g/m², and/or    -   a thickness of from 0.1 to 0.6 mm, in particular from 0.2 to        0.5, and/or    -   a lengthwise ultimate tensile stress elongation of from 400 to        700%, and/or    -   a transverse ultimate tensile stress elongation of from 250 to        550%.

As carrier material it is also possible to use all known textilecarriers such as wovens, knits or nonwoven webs; the term “web” embracesat least textile sheetlike structures in accordance with EN 29092 (1988)and also stitchbonded nonwovens and similar systems.

It is likewise possible to use spacer fabrics, including spacer knits,with lamination. Spacer fabrics of this kind are disclosed in EP 0 071212 B1. Spacer fabrics are matlike layer structures comprising a coverlayer of a fiber or filament web, an underlayer and individual retainingfibers or bundles of such fibers between these layers, said fibers beingdistributed over the area of the layer structure, being needled throughthe particle layer, and joining the cover layer and the underlayer toone another. As an additional, though not mandatory, feature, theretaining fibers in accordance with EP 0 071 212 B1comprise inertmineral particles, such as sand, gravel or the like, for example.

The holding fibers needled through the particle layer hold the coverlayer and the underlayer at a distance from one another and are joinedto the cover layer and the underlayer.

Spacer wovens or spacer knits are described, inter alia, in twoarticles, namely

-   -   an article from the journal “kettenwirk-praxis 3/93”, 1993,        pages 59 to 63, “Raschelgewirkte Abstandsgewirke”        [Raschel-knitted spacer knits]        and    -   an article from the journal “kettenwirk-praxis 1/94”, 1994,        pages 73 to 76, “Raschelgewirkte Abstandsgewirke”,        the content of said articles being included here by reference        and being part of this disclosure and invention.

Suitable nonwovens include, in particular, consolidated staple fiberwebs, but also filament webs, meltblown webs, and spunbonded webs, whichgenerally require additional consolidation. Possible consolidationmethods for webs are mechanical, thermal, and chemical consolidation.Whereas with mechanical consolidations the fibers are held togetherpurely mechanically, usually by entanglement of the individual fibers,by the interlooping of fiber bundles or by the stitching-in ofadditional threads, it is possible by thermal and by chemical techniquesto obtain adhesive (with binder) or cohesive (binderless) fiber-fiberbonds. Given appropriate formulation and an appropriate process regime,these bonds may be restricted exclusively, or at least predominantly, tofiber nodal points, so that a stable, three-dimensional network isformed while retaining the loose, open structure in the web.

Webs which have proven particularly advantageous are those consolidatedin particular by overstitching with separate threads or by interlooping.

Consolidated webs of this kind are produced, for example, onstitchbonding machines of the “Malifleece” type from the company KarlMeyer, formerly Malimo, and can be obtained, inter alia, from thecompanies Naue Fasertechnik and Techtex GmbH. A Malifleece ischaracterized in that a cross-laid web is consolidated by the formationof loops from fibers of the web.

The carrier used may also be a web of the Kunit or Multiknit type. AKunit web is characterized in that it originates from the processing ofa longitudinally oriented fiber web to form a sheetlike structure whichhas the heads and legs of loops on one side and, on the other, loop feetor pile fiber folds, but possesses neither threads nor prefabricatedsheetlike structures. A web of this kind has been produced, inter alia,for many years, for example on stitchbonding machines of the“Kunitvlies” type from the company Karl Mayer. A further characterizingfeature of this web is that, as a longitudinal-fiber web, it is able toabsorb high tensile forces in the longitudinal direction. Thecharacteristic feature of a Multiknit web relative to the Kunit is thatthe web is consolidated on both the top and bottom sides by virtue ofdouble-sided needle punching.

Finally, stitchbonded webs are also suitable as an intermediate forforming an adhesive tape of the invention. A stitchbonded web is formedfrom a nonwoven material having a large number of stitches extendingparallel to one another. These stitches are brought about by theincorporation, by stitching or knitting, of continuous textile threads.For this type of web, stitchbonding machines of the “Maliwatt” type fromthe company Karl Mayer, formerly Malimo, are known.

Also particularly advantageous is a staple fiber web which ismechanically preconsolidated in the first step or is a wet-laid web laidhydrodynamically, in which between 2% and 50% of the web fibers arefusible fibers, in particular between 5% and 40% of the fibers of theweb.

A web of this kind is characterized in that the fibers are laid wet or,for example, a staple fiber web is preconsolidated by the formation ofloops from fibers of the web or by needling, stitching or air-jet and/orwater-jet treatment.

In a second step, thermofixing takes place, with the strength of the webbeing increased again by the (partial) melting of the fusible fibers.

The web carrier may also be consolidated without binders, by means forexample of hot embossing with structured rollers, with properties suchas strength, thickness, density, flexibility, and the like beingcontrollable via pressure, temperature, residence time, and embossinggeometry.

For the inventive use of nonwovens, the adhesive consolidation ofmechanically preconsolidated or wet-laid webs is of particular interest,it being possible for said consolidation to take place by way of theaddition of binder in solid, liquid, foamed or pastelike form. A greatdiversity of theoretical embodiments is possible: for example, solidbinders as powders for trickling in, as a sheet or as a mesh, or in theform of binding fibers. Liquid binders may be applied as solutions inwater or organic solvent or as a dispersion. For adhesive consolidation,binder dispersions are predominantly chosen: thermosets in the form ofphenolic or melamine resin dispersions, elastomers as dispersions ofnatural or synthetic rubbers, or, usually, dispersions of thermoplasticssuch as acrylates, vinyl acetates, polyurethanes, styrene-butadienesystems, PVC, and the like, and also copolymers thereof. Normally, thedispersions are anionically or nonionically stabilized, although incertain cases cationic dispersions may also be of advantage.

The binder may be applied in a manner which is in accordance with theprior art and for which it is possible to consult, for example, standardworks of coating or of nonwoven technology such as “Vliesstoffe” (GeorgThieme Verlag, Stuttgart, 1982) or “Textiltechnik-Vliesstofferzeugung”(Arbeitgeberkreis Gesamttextil, Eschborn, 1996).

For mechanically preconsolidated webs which already possess sufficientcomposite strength, the single-sided spray application of a binder isappropriate for effecting specific changes in the surface properties.

Such a procedure is not only sparing in its use of binder but alsogreatly reduces the energy requirement for drying. Since no squeezerolls are required and the dispersion remains predominantly in the upperregion of the web material, unwanted hardening and stiffening of the webcan largely be avoided.

For sufficient adhesive consolidation of the web carrier, the additionof binder in the order of magnitude of from 1% to 50%, in particularfrom 3% to 20%, based on the weight of the fiber web, is generallyrequired.

The binder may be added as early as during the manufacture of the web,in the course of mechanical preconsolidation, or else in a separateprocess step, which may be carried out in line or off line. Followingthe addition of a binder it is necessary temporarily to generate a statein which the binder becomes adhesive and adhesively connects thefibers—this may be achieved during the drying, for example, ofdispersions, or else by heating, with further possibilities forvariation existing by way of area or partial application of pressure.The binder may be activated in known drying tunnels, or else, given anappropriate selection of binder, by means of infrared radiation, UVradiation, ultrasound, high-frequency radiation or the like. For thesubsequent end use it is sensible, although not absolutely necessary,for the binder to have lost its tack following the end of the webproduction process.

A further, special form of adhesive consolidation consists in activatingthe binder by incipient dissolution or swelling. In this case it is alsopossible in principle for the fibers themselves, or admixed specialfibers, to take over the function of the binder. Since, however, suchsolvents are objectionable on environmental grounds, and/or areproblematic in their handling, for the majority of polymeric fibers,this process is not often employed.

Starting materials envisaged for the textile carrier include, inparticular, polyester, polypropylene, viscose or cotton fibers. Thepresent invention is, however, not restricted to said materials; ratherit is possible to use a large number of other fibers to produce the web,as is evident to the skilled worker without any need for inventiveactivity.

Moreover, knitted fabrics are also outstandingly suitable. Knittedfabrics are produced from one or more threads or thread systems byintermeshing (interlooping), in contrast to woven fabrics, which areproduced by intersecting two thread systems (warp and weft threads), andnonwovens (bonded fiber fabrics), where a loose fiber web isconsolidated by heat, needling or stitching or by means of water jets.

Knitted fabrics can be divided into weft knits, in which the threads runin transverse direction through the textile, and warp knits, where thethreads run lengthwise through the textile. As a result of their meshstructure, knitted fabrics are fundamentally pliant, conformingtextiles, since the meshes are able to stretch lengthways and widthways,and have a tendency to return to their original position. In high-gradematerial, they are very robust.

Finally, the web-form material may be a material with an antiadhesivecoating on both sides, such as a release paper or a release film. Ifdesired, the coated backing material is lined with a further releasefilm or a further release paper.

The thickness of the self-adhesive composition on the web-form materialmay be between 10 μm and 2,000 μm, preferably between 20 μm and 500 μm,with particular preference between 50 and 400 μm.

EXAMPLES

The intention of the examples which follow is to describe the inventionin more detail, without wishing thereby to restrict the invention.

Example 1

A prototype of a self-adhesive composition doped with active substancewas prepared solventlessly and continuously using a twin screw extruder,employing the following exemplary formulation (all amounts in parts perhundred (phr) based on the sum of the block copolymer fraction):

-   A) 100.0 phr A-B/A-B-A block copolymer, consisting of hard and soft    segments, with a ratio of A-B-A to A-B of 41:9 and a styrene content    of 15% by mass (Vector 4113, Dexco)-   B) 21.5 phr hydrocarbon resin (Wingtack 95, Goodyear)-   C) 23.9 phr polyterpene resin (Sylvares TR 7115, Arizona Chemical)-   D) 17.9 phr rosin ester resin (Staybelite Ester 10, Eastman)-   E) 29.9 phr filler (rice flour/iris powder)-   F) 9.6 phr paraffinic mineral oil (Ondina 917, Shell Chemicals)-   G) 4.8 phr aging inhibitor (Vulkanox BKF, Bayer)-   H) 17.9 phr lanolin DAB [German Pharmacopoeia]-   I) 13.6 phr capsicum extract as active hyperemic substance,    corresponding to 0.3 phr capsaicinoids (calculated as capsaicin)

Example 2

A doped self-adhesive composition was prepared as in example 1 inaccordance with the following exemplary formulation (all amounts inparts per hundred (phr) based on the sum of the block copolymerfraction):

-   A) 100.0 phr A-B/A-B-A block copolymer, consisting of hard and soft    segments, with a ratio of A-B-A to A-B of 14:11 and a styrene    content of 16% by mass (Kraton D-1113, Kraton)-   B) 59.9 phr hydrocarbon resin (Escorez 2203, ExxonMobil)-   D) 46.1 phr hydrocarbon resin (Arkon P90, Arakawa)-   F) 7.8 phr mineral oil (Whitemor WOM 14, Castrol Ltd.)-   G) 3.4 phr aging inhibitor (Irganox 1010, Ciba Specialty Chemicals)-   H) 12.2 phr plasticizer (Cetiol V. Henkel KGaA)-   J) 0.16 phr nonyl vanillylamide as active substance

Example 3

Another prototype of a self-adhesive composition doped with activesubstance was prepared solventlessly and continuously by the sameprocedure as in example 1. In this case the following exemplaryformulation was employed (all amounts in parts per hundred (phr) basedon the sum of the block copolymer fraction):

-   A) 100.0 phr A-B/A-B-A block copolymer, consisting of hard and soft    segments, with a ratio of A-B-A to A-B of 29:21 and a styrene    content of 15% by mass (Vector 4114, Dexco)-   C) 22.7 phr hydrogenated hydrocarbon resin (Escorez 5380,    ExxonMobil)-   D) 55.9 phr hydrogenated rosin (Foral AX-E, Eastman)-   F) 7.3 phr mineral oil (Pionier 2071, Hansen&Rosenthal)-   G) 2.6 phr aging inhibitor (Lowinox 22M46, Great Lakes Chemical    Corp.)-   H) 8.9 phr plasticizer (Cetiol V, Henkel KGaA)-   I) 18.6 phr capsicum extract as active hyperemic substance,    corresponding to 0.4 phr of capsaicinoids (calculated as capsaicin)

Procedure

The prototypes were produced with the aid of a twin screw extruder fromLeistritz, having a screw diameter of 50 mm. The backing material wascoated using a slot die. FIG. 1 shows a diagrammatic overview of theunit used to carry out the method.

Raw materials A and G were each supplied via a gravimetric meteringsystem (I) and (II) to the filling section of a twin screw extruder.

The material was supplied via a first conveying process zone (1) tofurther zones (2)-(4), which mixed the material.

In the conveying process zone (5)—depending on formulation—componentsB/C/D were metered in gravimetrically (III). This was followed by mixingand conveying (6).

Thereafter came zone (7), which conveyed the material and to whichcomponents F and—depending on formulation—H, or a homogeneous mixture orsolution of H and J, were metered by way of volumetrically operatinggear pumps (IV) and (V). Thereafter the material was mixed again.

This was followed by zone (8), which conveyed the material and towhich—depending on formulation—component E was metered by way of agravimetric metering system (VI) and component I by way of avolumetrically operating gear pump (VII).

In zones (9)-(11) the material was mixed and conveyed.

Subsequently the self-adhesive composition was shaped by way of a 350 mmslot die (12) and extruded. Calendering took place in a calender unit(13), along with lamination to two PET films.

The rotary speed of the extruder was between 100 and 150 rpm. At theexit from the extruder the composition had a temperature of between 90°C. and 100° C.

Analysis

From the laboratory specimens, 5 samples in each case with a diameter of2.2 cm were punched out and investigated for their release behavior onpig's skin.

For this purpose a sample was applied to a section of pig's skin whichhad been placed on a Franz release vessel. The release vessel was filledwith a receptor phase which was temperature-controlled at a constant35.5° C. and was stirred continuously. After 24 h the level ofcapsaicinoids in the skin and in the receptor phase was determinedquantitatively.

The patch produced from the composition described in example 1 showedeffective release of the active substance. Under the conditionsspecified above, 14 parts per thousand of the active substance wereabsorbed dermally. The standardized, relative fraction of the dermallyabsorbed amount is subdivided as follows:

-   -   1.6% in the horny layer    -   44.2% in the epidermis    -   52.2% in the dermis    -   2.0% in the receptor phase.

1-11. (canceled)
 12. A process for a solvent-free and mastication-freeproduction of a self-adhesive SBC-based composition which comprises atleast one pharmaceutically active substance, in a continuously operatingapparatus which comprises a feeding section and a compounding section,said process comprising (a) feeding an initial batch which comprisesSBC, at least a part of the at least one pharmaceutically activesubstance and, optionally, at least a part of any further components ofthe composition into the feeding section of the apparatus; (b)transferring the initial batch from the feeding section to thecompounding section of the apparatus; (c) optionally, adding anyremaining part of the at least one pharmaceutically active substance andany remaining part of the further components of the composition whichhave not been added to the feeding section, to the compounding section;(d) treating the composition in the compounding section to prepare ahomogeneous self-adhesive composition; and (e) discharging thehomogeneous self-adhesive composition from the apparatus.
 13. Theprocess of claim 12, wherein the further components of the compositionare selected from one or more of low molecular weight SBCs, fillers,plasiticizers, tackifiers, resins, release aids and additives.
 14. Theprocess of claim 12, wherein the apparatus comprises a twin-screwextruder.
 15. The process of claim 14, wherein the twin-screw extrudercomprises at least one metering port and at least one degassing port.16. The process of claim 15, wherein the twin-screw extruder comprisesfrom two to seven metering ports.
 17. The process of claim 12, wherein atemperature inside the apparatus is from 85° C. to 120° C.
 18. Theprocess of claim 17, wherein the temperature is up to 110° C.
 19. Theprocess of claim 18, wherein the temperature is up to 100° C.
 20. Theprocess of claim 12, wherein the at least one pharmaceutically activesubstance is used in a concentration of from 0.001% to 0.70% by weight,based on the weight of the composition.
 21. The process of claim 20,wherein the at least one pharmaceutically active substance is used in aconcentration of from 0.01% to 0.67% by weight.
 22. The process of claim21, wherein the at least one pharmaceutically active substance is usedin a concentration of from 0.03% to 0.63% by weight.
 23. The process ofclaim 12, wherein the SBC is used in a concentration of from 5% to 90%by weight.
 24. The process of claim 22, wherein the SBC is used in aconcentration of from 10% to 85% by weight.
 25. A process for asolvent-free and mastication-free production of a self-adhesiveSBC-based composition which comprises at least one pharmaceuticallyactive substance, in a continuously operating apparatus which comprisesa feeding section and a compounding section, said process comprising (a)feeding an initial batch which comprises SBC and, optionally, at least apart of any further components of the composition with the exception ofthe at least one pharmaceutically active substance into the feedingsection of the apparatus; (b) transferring the initial batch from thefeeding section to the compounding section of the apparatus; (c) addingthe at least one pharmaceutically active substance and, optionally, anyremaining part of the further components of the composition which hasnot been added to the feeding section to the compounding section; (d)treating the composition in the compounding section to prepare ahomogeneous self-adhesive composition; and (e) discharging thehomogeneous self-adhesive composition from the apparatus.
 26. Theprocess of claim 25, wherein the further components of the compositionare selected from one or more of low molecular weight SBCs, fillers,plasiticizers, tackifiers, resins, release aids and additives.
 27. Theprocess of claim 25, wherein the apparatus comprises a twin-screwextruder.
 28. The process of claim 27, wherein the twin-screw extrudercomprises at least one metering port and at least one degassing port.29. The process of claim 28, wherein the twin-screw extruder comprisesfrom two to seven metering ports.
 30. The process of claim 25, wherein atemperature inside the apparatus is from 85° C. to 120° C.
 31. Theprocess of claim 30, wherein the temperature is up to 110° C.
 32. Theprocess of claim 31, wherein the temperature is up to 100° C.
 33. Theprocess of claim 25, wherein the at least one pharmaceutically activesubstance is used in a concentration of from 0.001% to 0.70% by weight,based on the weight of the composition.
 34. The process of claim 33,wherein the at least one pharmaceutically active substance is used in aconcentration of from 0.01% to 0.67% by weight.
 35. The process of claim34, wherein the at least one pharmaceutically active substance is usedin a concentration of from 0.03% to 0.63% by weight.
 36. The process ofclaim 25, wherein the SBC is used in a concentration of from 5% to 90%by weight.
 37. The process of claim 35, wherein the SBC is used in aconcentration of from 10% to 85% by weight.
 38. A self-adhesivecomposition which is obtainable by the process of claim
 12. 39. Aself-adhesive composition which is obtainable by the process of claim25.
 40. A process for producing a self-adhesive composition on a carriermaterial, which process comprises carrying out the process of claim 12,transferring the self-adhesive composition to a coating device andthereafter, coating the carrier material with the self-adhesive coatingcomposition.
 41. The process of claim 40, wherein the transfer of thecoating composition to the coating device involves at least one of amelt pump and an extruder.
 42. The process of claim 40, wherein thecarrier material comprises a web material.
 43. The process of claim 40,wherein the carrier material comprises at least one of a release filmand a release paper.
 44. The process of claim 43, wherein the processfurther comprises covering the coated composition with a release film orrelease paper.
 45. The process of claim 40, wherein the coating devicecomprises an extrusion die.
 46. The process of claim 40, wherein thecoating device comprises at least one of a roll unit and a calenderunit.
 47. The process of claim 46, wherein a coating thickness of thecomposition is adjusted by allowing it to pass through one or more rollnips of the at least one of a roll unit and a calender unit.
 48. Theprocess of claim 46, wherein the coating device further comprises anextrusion die.
 49. The process of claim 40, wherein a thickness of theself-adhesive composition on the carrier material is adjusted to from 10μm to 2,000 μm.
 50. The process of claim 49, wherein the thickness isfrom 20 μm to 500 μm.
 51. The process of claim 50, wherein the thicknessis from 50 μm to 400 μm.
 52. A process for producing a self-adhesivecomposition on a carrier material, which process comprises carrying outthe process of claim 25, transferring the self-adhesive composition to acoating device and thereafter, coating the carrier material with theself-adhesive coating composition.
 53. The process of claim 52, whereinthe transfer of the coating composition to the coating device involvesat least one of a melt pump and an extruder.
 54. The process of claim52, wherein the carrier material comprises a web material.
 55. Theprocess of claim 52, wherein the carrier material comprises at least oneof a release film and a release paper.
 56. The process of claim 45,wherein the process further comprises covering the coated compositionwith one of a release film and a release paper.
 57. The process of claim52, wherein the coating device comprises an extrusion die.
 58. Theprocess of claim 52, wherein the coating device comprises at least oneof a roll unit and a calender unit.
 59. The process of claim 58, whereina coating thickness of the composition is adjusted by allowing it topass through one or more roll nips of the at least one of a roll unitand a calender unit.
 60. The process of claim 48, wherein the coatingdevice further comprises an extrusion die.
 61. The process of claim 52,wherein a thickness of the self-adhesive composition on the carriermaterial is adjusted to from 10 μm to 2,000 μm.
 62. The process of claim61, wherein the thickness is from 20 μm to 500 μm.
 63. The process ofclaim 62, wherein the thickness is from 50 μm to 400 μm.
 64. Aself-adhesive composition on a carrier material which is obtainable bythe process of claim
 40. 65. A self-adhesive composition on a carriermaterial which is obtainable by the process of claim 52.